Current surface coating technology provides a relatively limited number of established surfaces that may be used in new solid-phase chemical or biochemical applications. The lack of established surfaces stems primarily from the difficulty associated with the generation of different surface coatings. While large numbers of chemically diverse compounds may now be generated in solution without too much difficulty, the ability to graft these molecules on to a solid phase and create a large number of surface coatings has proven a much more difficult problem to solve. In particular, the chemistry of grafting molecules onto solid phases to create surface coatings is highly unpredictable, and has to date remained more an art than a science.
There are numerous applications where a diverse range of novel surface coatings would be particularly advantageous, for example in the area of solid phase biological assays. With the number of novel proteins growing each day, there is growing need for novel solid phase surfaces that are compatible with the immobilization of these complex macromolecules. Despite this need, in practice there are to date relatively few solid surfaces available across the wide range of solid phase applications used to study biological molecules. For example, in the area of capture and display of biomolecules each commercial supplier has its own particular solid phase surface embodiment that is prescribed across a broad range of specific applications. One specific example is a surface generated using the well-established PEG chemistry as described in an article by Ruiz-Taylor et al. (“Monolayers of derivatized poly(L-lysine)-grafted poly(ethylene glycol) on metal oxides as a class of biomolecular interfaces,” PNAS USA 98: 852-857 (2001)). Another example is the relatively new boronic acid complex chemistry used to prepare surfaces for immobilization of proteins described by Stolowitz et al. (“Phenylboronic Acid-Salicylhydroxamic Acid Bioconjugates. 1. A Novel Boronic Acid Complex for Protein Immobilization,” Bioconjugate Chemistry 12: 229-239 (2001)).
Surface plasmon resonance (SPR) has now been widely adopted as a technique for detecting protein-ligand and protein-protein binding interactions. However the utility of SPR with a particular protein system depends greatly on the vagaries of how that macromolecule binds to the surface of the solid substrate when immobilized. If a particular SPR surface causes a protein of interest to bind in an orientation that is unfavorable for detecting ligand binding, there are only a handful of alternative surfaces with a limited range of binding properties from which to choose (see, e.g. Rich and Myszka “Advances in surface plasmon resonance biosensor analysis,” Current Opinion in Biotechnology 11: 54-61 (2000)).
Similarly, mass spectrometry also is now widely employed for the analysis of biological macromolecules. These methods typically involve immobilization of a protein on a surface of substrate where it is then exposed to a ligand binding interaction. Following ligand binding (or non-binding) the molecule is desorbed from the surface and into a spectrometer using a laser (see, e.g. Merchant and Weinberger, “Recent advancements in surface-enhanced laser desorption/ionization-time of flight-mass spectrometry,” Electrophoresis 21: 1164-1177 (2000)). As in the SPR experiment, the success of the mass spectrometry experiment depends largely on the interaction between the immobilized protein and the surface. In view of the thousands of proteins with different surface interactions, there is clearly a need for a large number of different substrate surfaces in order for mass spectrometry to be applied successfully to the high throughput analysis of the proteome.
Accordingly, the inability to provide a diverse array of surface coatings stands as an impediment to development in solid phase biological technologies such as biological assays and diagnostics, and biomaterials. Such an impediment also extends across a broad spectrum of other technologies, ranging from solid-phase chemical synthesis, catalysis development and separation and purification technologies.